Reaching back to enhance the future: the American Association for the Surgery of Trauma Diversity, Equity and Inclusion Pipeline Program.

Objectives: There are significant disparities in the surgical workforce in comparison with medical student demographics. Pipeline programs have shown to be effective in addressing gaps. The American Association for the Surgery of Trauma Diversity, Equity and Inclusion Committee designed a longitudinal pipeline program with high school student mentees and surgeon mentors providing an in-person hands-on workshop. Methods: The mentee demographics and socioeconomic status at the time of application were determined using overall percentages and the Area Deprivation Index (ADI). Program application essays were qualitatively analyzed for common themes. The pre-workshop and post-workshop and 6-month follow-up surveys were analyzed for mentee experience and areas for improvement. Results: Mentees selected were 30% male (N=3 of 10), 70% female (N=7 of 10), 50% black or African American (N=5 of 10) and 30% Hispanic or Latinx (N=3 of 10). The majority of mentees were in the most disadvantaged groups in their state by the ADI (N=8 of 9, 89%). Many of the application essays highlighted a personal loss as driving the interest in a health career with several of those losses based on 'gun violence'. There was under-representation in medicine racial/ethnic or gender concordance for 80% (N=8 of 10) of the mentee-mentor pairings. In the pre-workshop survey, even those students with high-grade point averages and strong academic achievement in science courses indicated low confidence in their ability to succeed. Most students (N=7 of 10, 70%) reported a strong positive connection with their mentor in the post-workshop survey. There was a reduction in self-identified modifiable barriers to success for 83% (N=5 of 6) of the mentees. One-third of students who responded to the 6-month survey indicated that they had issues with maintaining contact with their mentors after the workshop. Conclusion: The pipeline program was able to reach the target demographic and increase interest in surgery. Positive mentee/mentor relationships were formed. There are improvements to be made in longitudinal components of the program to ensure lasting results. Level of evidence: III.

Disability reduction following a lumbar stabilization exercise program for low back pain: large vs. small improvement subgroup analyses of physical and psychological variables.

BACKGROUND: Little is known about why patients with low back pain (LBP) respond differently to treatment, and more specifically, to a lumbar stabilization exercise program. As a first step toward answering this question, the present study evaluates how subgroups of patients who demonstrate large and small clinical improvements differ in terms of physical and psychological changes during treatment. METHODS: Participants (n = 110) performed the exercise program (clinical sessions and home exercises) over eight weeks, with 100 retained at six-month follow-up. Physical measures (lumbar segmental instability, motor control impairments, range of motion, trunk muscle endurance and physical performance tests) were collected twice (baseline, end of treatment), while psychological measures (fear-avoidance beliefs, pain catastrophizing, psychological distress, illness perceptions, outcome expectations) were collected at four time points (baseline, mid-treatment, end of treatment, follow-up). The participants were divided into three subgroups (large, moderate and small clinical improvements) based on the change of perceived disability scores. ANOVA for repeated measure compared well-contrasted subgroups (large vs. small improvement) at different times to test for SUBGROUP × TIME interactions. RESULTS: Statistically significant interactions were observed for several physical and psychological measures. In all these interactions, the large- and small-improvement subgroups were equivalent at baseline, but the large-improvement subgroup showed more improvements over time compared to the small-improvement subgroup. For psychological measures only (fear-avoidance beliefs, pain catastrophizing, illness perceptions), between-group differences reached moderate to strong effect sizes, at the end of treatment and follow-up. CONCLUSIONS: The large-improvement subgroup showed more improvement than the small-improvement subgroup with regard to physical factors typically targeted by this specific exercise program as well as for psychological factors that are known to influence clinical outcomes.

Maximizing wound coverage in full-thickness skin defects: A randomized-controlled trial of autologous skin cell suspension and widely meshed autograft versus standard autografting.

BACKGROUND: Traumatic insults, infection, and surgical procedures can leave skin defects that are not amenable to primary closure. Split-thickness skin grafting (STSG) is frequently used to achieve closure of these wounds. Although effective, STSG can be associated with donor site morbidity, compounding the burden of illness in patients undergoing soft tissue reconstruction procedures. With an expansion ratio of 1:80, autologous skin cell suspension (ASCS) has been demonstrated to significantly decrease donor skin requirements compared with traditional STSG in burn injuries. We hypothesized that the clinical performance of ASCS would be similar for soft tissue reconstruction of nonburn wounds. METHODS: A multicenter, within-patient, evaluator-blinded, randomized-controlled trial was conducted of 65 patients with acute, nonthermal, full-thickness skin defects requiring autografting. For each patient, two treatment areas were randomly assigned to concurrently receive a predefined standard-of-care meshed STSG (control) or ASCS + more widely meshed STSG (ASCS+STSG). Coprimary endpoints were noninferiority of ASCS+STSG for complete treatment area closure by Week 8, and superiority for relative reduction in donor skin area. RESULTS: At 8 weeks, complete closure was observed for 58% of control areas compared with 65% of ASCS+STSG areas (p = 0.005), establishing noninferiority of ASCS+STSG. On average, 27.4% less donor skin was required with ASCS+ STSG, establishing superiority over control (p < 0.001). Clinical healing (≥95% reepithelialization) was achieved in 87% and 85% of Control and ASCS+STSG areas, respectively, at 8 weeks. The treatment approaches had similar long-term scarring outcomes and safety profiles, with no unanticipated events and no serious ASCS device-related events. CONCLUSION: ASCS+STSG represents a clinically effective and safe solution to reduce the amount of skin required to achieve definitive closure of full-thickness defects without compromising healing, scarring, or safety outcomes. This can lead to reduced donor site morbidity and potentially decreased cost associated with patient care.Clincaltrials.gov identifier: NCT04091672. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level I.

Physical activity for patients with chronic low back pain: What are physical therapists prescribing?

BACKGROUND: Despite the extensive evidence supporting physical activity (PA) for managing chronic low back pain (CLBP), little is known about PA prescription by physical therapists treating patients with CLBP. OBJECTIVE: 1) Explore how PA prescriptions provided by outpatient physical therapists treating patients with CLBP align with PA guidelines. 2) Examine the barriers and facilitators of PA prescription among physical therapists working with patients with CLBP. METHODS: We conducted a qualitative study with outpatient physical therapists who treat CLBP. Semi-structured interviews provided an understanding of physical therapist experience with PA prescription among patients with CLBP. The interviews were transcribed, coded, and analyzed thematically. RESULTS: The 18 participants had an average of 13.4 (6.4) years of clinical experience in outpatient physical therapy. Thematic analysis revealed: 1) Physical therapists' articulate knowledge of PA guidelines and importance of physical activity; 2) Patient factors take priority over the PA guidelines for people with CLBP; and 3) The importance of building and maintaining a strong patient-therapist relationship influences physical therapist prescription of PA for patients with CLBP. CONCLUSION: When providing PA recommendations for patients with CLBP, general movement recommendations are emphasized in place of explicit PA prescriptions. Our findings highlight factors for consideration when prescribing movement and PA for patients with CLBP.

The relationship between clinical examination measures and ultrasound measures of fascia thickness surrounding trunk muscles or lumbar multifidus fatty infiltrations: An exploratory study.

Patients with chronic low back pain (CLBP) exhibit remodelling of the lumbar soft tissues such as muscle fatty infiltrations (MFI) and fibrosis of the lumbar multifidus (LuM) muscles, thickness changes of the thoracolumbar fascia (TLF) and perimuscular connective tissues (PMCT) surrounding the abdominal lateral wall muscles. Rehabilitative ultrasound imaging (RUSI) parameters such as thickness and echogenicity are sensitive to this remodelling. This experimental laboratory study aimed to explore whether these RUSI parameters (LuM echogenicity and fascia thicknesses), hereafter called dependent variables (DV) were linked to independent variables (IV) such as (1) other RUSI parameters (trunk muscle thickness and activation) and (2) physical and psychological measures. RUSI measures, as well as a clinical examination comprising physical tests and psychological questionnaires, were collected from 70 participants with LBP. The following RUSI dependent variables (RUSI-DV), measures of passive tissues were performed bilaterally: (1) LuM echogenicity (MFI/fibrosis) at three vertebral levels (L3/L4, L4/L5 and L5/S1); (2) TLF posterior layer thickness, and (3) PMCT thickness of the fasciae between subcutaneous tissue thickness (STT) and external oblique (PMCTSTT/EO ), between external and internal oblique (PMCTEO/IO ), between IO and transversus abdominis (PMCTIO/TrA ) and between TrA and intra-abdominal content (PMCTTrA/IA ). RUSI measures of trunk muscle's function (thickness and activation), also called measures of active muscle tissues, were considered as independent variables (RUSI-IV), along with physical tests related to lumbar stability (n = 6), motor control deficits (n = 7), trunk muscle endurance (n = 4), physical performance (n = 4), lumbar posture (n = 2), and range of motion (ROM) tests (n = 6). Psychosocial measures included pain catastrophizing, fear-avoidance beliefs, psychological distress, illness perceptions and concepts related to adherence to a home-based exercise programme (physical activity level, self-efficacy, social support, outcome expectations). Six multivariate regression models (forward stepwise selection) were generated, using RUSI-DV measures as dependent variables and RUSI-IV/physical/psychosocial measures as independent variables (predictors). The six multivariate models included three to five predictors, explaining 63% of total LuM echogenicity variance, between 41% and 46% of trunk superficial fasciae variance (TLF, PMCTSTT/EO ) and between 28% and 37% of deeper abdominal wall fasciae variance (PMCTEO/IO , PMCTIO/TrA and PMCTTrA/IA ). These variables were from RUSI-IV (LuM thickness at rest, activation of IO and TrA), body composition (percent fat) and clinical physical examination (lumbar and pelvis flexion ROM, aberrant movements, passive and active straight-leg raise, loaded-reach test) from the biological domain, as well as from the lifestyle (physical activity level during sports), psychological (psychological distress-cognitive subscale, fear-avoidance beliefs during physical activities, self-efficacy to exercise) and social (family support to exercise) domains. Biological, psychological, social and lifestyle factors each accounted for substantial variance in RUSI-passive parameters. These findings are in keeping with a conceptual link between tissue remodelling and factors such as local and systemic inflammation. Possible explanations are discussed, in keeping with the hypothesis-generating nature of this study (exploratory). However, to impact clinical practice, further research is needed to determine if the most plausible predictors of trunk fasciae thickness and LuM fatty infiltrations have an effect on these parameters.

Outcomes and Factors Associated with Occult Septic Shock in Emergency Department Patients with Soft Tissue Infection.

Introduction: Patients who develop occult septic shock (OSS) are associated with worse outcomes than those with early septic shock (ESS). Patients with skin and soft tissue infection (SSTI) may have underlying organ dysfunction due to OSS, yet the prevalence and the outcomes of patients with SSTI and early versus occult shock have not been described. This study compared the clinical characteristics of SSTI patients and the prevalence of having no septic shock (NSS), ESS, or OSS. Methods: We retrospectively analyzed charts of adult patients who were transferred from any emergency department to our academic center between January 1, 2014, and December 31, 2016. Outcomes of interest were the development of OSS and acute kidney injury (AKI). We performed logistic regressions to measure the association between clinical factors with the outcomes and created probability plots to show the relationship between key clinical variables and outcomes of OSS or AKI. Results: Among 269 patients, 218 (81%) patients had NSS, 16 (6%) patients had ESS, and 35 (13%) patients had OSS. Patients with OSS had higher mean serum lactate concentrations than patients with NSS (3.5 vs. 2.1 mmol/L, P < 0.01). Higher sequential organ failure assessment (SOFA) score was associated with higher likelihood of developing OSS (odds ratio [OR] 1.41, 95% confidence interval [CI] 1.23-1.62, P < 0.001). NSS was associated with very low odds of developing AKI (OR 0.16, 95% CI 0.08-0.33, P < 0.001). Conclusions: 13% of the patients with SSTI developed OSS. Patients with OSS had elevated serum lactate concentration and higher SOFA score than those with NSS. Increased SOFA score is a predictor for the development of OSS.

Is There a Place for Hyperbaric Oxygen Therapy?

Hyperbaric oxygen therapy (HBOT) involves treating patients by providing 100% oxygen through inhalation while inside a treatment pressurized chamber. The oxygen acts as a drug and the hyperbaric chamber as the dosing device. The effect of hyperbaric hyperoxia is dose dependent and, therefore, treatment depth and duration are important when considering its use. HBOT can either be the primary method of treatment or used adjunctively to medications or surgical techniques. The underpinning physiology is to bring oxygen-rich plasma to hypoxic tissue, preventing reperfusion injury, strengthening immune responsiveness, and encouraging new collagen deposition as well as endothelial cell formation.

Derivation of clinical prediction rules for identifying patients with non-acute low back pain who respond best to a lumbar stabilization exercise program at post-treatment and six-month follow-up.

Low back pain (LBP) remains one of the most common and incapacitating health conditions worldwide. Clinical guidelines recommend exercise programs after the acute phase, but clinical effects are modest when assessed at a population level. Research needs to determine who is likely to benefit from specific exercise interventions, based on clinical presentation. This study aimed to derive clinical prediction rules (CPRs) for treatment success, using a lumbar stabilization exercise program (LSEP), at the end of treatment and at six-month follow-up. The eight-week LSEP, including clinical sessions and home exercises, was completed by 110 participants with non-acute LBP, with 100 retained at the six-month follow-up. Physical (lumbar segmental instability, motor control impairments, posture and range of motion, trunk muscle endurance and physical performance tests) and psychological (related to fear-avoidance and home-exercise adherence) measures were collected at a baseline clinical exam. Multivariate logistic regression models were used to predict clinical success, as defined by ≥50% decrease in the Oswestry Disability Index. CPRs were derived for success at program completion (T8) and six-month follow-up (T34), negotiating between predictive ability and clinical usability. The chosen CPRs contained four (T8) and three (T34) clinical tests, all theoretically related to spinal instability, making these CPRs specific to the treatment provided (LSEP). The chosen CPRs provided a positive likelihood ratio of 17.9 (T8) and 8.2 (T34), when two or more tests were positive. When applying these CPRs, the probability of treatment success rose from 49% to 96% at T8 and from 53% to 92% at T34. These results support the further development of these CPRs by proceeding to the validation stage.

Global Survey of Demand-Side Factors and Incentives that Influence Advanced Trauma Life Support (ATLS) Promulgation.

BACKGROUND: We aimed to identify and describe demand-side factors that have been used to support ATLS global promulgation, as well as current gaps in demand-side incentives. METHODS: We performed a cross-sectional survey about demand-side factors that influence the uptake and promulgation of ATLS and other trauma-related CME courses. The survey was sent to each of the four global ATLS region chiefs and 80 ATLS country directors. Responses were described and qualitative data were analyzed using a content analysis framework. RESULTS: Representatives from 30 countries and each region chief responded to the survey (40% response rate). Twenty of 30 country directors (66%) reported that there were some form of ATLS verification requirements. ATLS completion, not current verification, was often the benchmark. Individual healthcare systems were the most common agency to require ATLS verification (37% of countries) followed by medical/surgical accreditation boards (33%), governments (23%), training programs (27%), and professional societies (17%). Multiple credentialing frameworks were reported including making ATLS verification a requirement for: emergency unit or trauma center designation (40%), contract renewal or promotion (37%); professional licensing (37%); training program graduation (37%); and increases in remuneration (3%). Unique demand-side incentives were reported including expansion of ATLS to non-physician cadre credentialing and use of subsidies. CONCLUSION: ATLS region chiefs and country directors reported a variety of demand-side incentives that may facilitate the promulgation of ATLS. Actionable steps include: (i) shift incentivization from ATLS course completion to maintenance of verification; (ii) develop an incentive toolkit of best practices to support implementation; and (iii) engage leadership stakeholders to use demand-side incentives to improve the training and capabilities of the providers they oversee to care for the injured.

Have Students Used Techniques to Stop the Bleed?

INTRODUCTION: The Stop the Bleed course was initiated in response to the Hartford Consensus and over 1 million people have been taught basic bleeding control techniques. Our study sought to determine the extent to which this training has been utilized. METHODS: Surveys were sent by email to students that had taken the Stop the Bleed course through our institution in 2017 or 2018. Data were collected utilizing the REDCap system and statistical calculations were performed. RESULTS: 2505 surveys were sent with 445 (18%) responses. The mean age of respondents was 48 years of age, 343 (77%) were female, and 230 (52%) were in the medical field. There were 17 respondents (3.8%) that stated they had utilized the techniques taught in the course; 16 out of 17 put pressure on a wound, 7 packed a wound, and 6 used a tourniquet. Patients had been injured by a variety of mechanisms including gunshot wound, stabbing, accidental laceration, and motor vehicle collision. Patients had good outcomes with 3 out of 17 surviving to emergency medical services arrival without known final outcome and the remaining 14 were known to do well. CONCLUSION: The Stop the Bleed course is important to enable bystanders to provide hemorrhage control. Our study shows that the techniques have been utilized with 17 treated patients having a good outcome and while a utilization rate of 3.8% may appear low, it is similar to the utilization rate of cardiopulmonary resuscitation instruction of 2%.

Lofty goals and strategic plans are not enough to achieve and maintain a diverse workforce: an American Association for the Surgery of Trauma Diversity, Equity, and Inclusion Committee conversation.

The American Association for the Surgery of Trauma Diversity, Equity, and Inclusion (DEI) Ad Hoc Committee organized a luncheon symposium with a distinguished panel of experts to discuss how to ensure a diverse surgical workforce. The panelists discussed the current state of DEI efforts within surgical departments and societal demographic changes that inform and necessitate surgical workforce adaptations. Concrete recommendations included the following: obtain internal data, establish DEI committee, include bias training, review hiring and compensation practices, support the department members doing the DEI work, commit adequate funding, be intentional with DEI efforts, and develop and support alternate pathways for promotion and tenure.

Dual goals of trunk restriction and stability are prioritized by individuals with chronic low back pain during a volitional movement.

BACKGROUND: Individuals with chronic low back pain demonstrate impaired responses to volitional and externally-generated postural perturbations that may impact stability whilst performing activities of daily living. Understanding how balance may be impaired by strategy selection is an important consideration during rehabilitation from low back pain to prevent future injurious balance loss. RESEARCH QUESTION: This cross-sectional study explored the influence of an active pain episode on volitional movement patterns and stability during a sit-to-stand task in individuals with chronic low back pain compared to those with no low back pain history. METHODS: Thirteen participants with low back pain who were in an active flare-up and 13 without pain sat on a height-adjusted chair and performed 5 sit-to-stand movements. Sagittal plane kinematics, kinetics, and surface electromyography were used to compute neuromuscular variables across Acceleration, Transition and Deceleration phases. Stability was assessed using times to contact of body centers of mass and pressure to base of support boundaries. Independent samples t-tests were used to examine group effects, and repeated measures analyses of variance assessed within-subjects effects across movement phases. RESULTS: Individuals with low back pain tended to restrict proximal joint motions through heightened muscle activity while increasing distal joint movement and distal muscle contributions. Individuals with low back pain used a greater driving force, indicated by a longer time to contact of the center of pressure, to achieve comparable center of mass stability. Individuals with low back pain may prioritize trunk restriction and stability through the sit-to-stand movement, possibly related to fear of pain or movement. SIGNIFICANCE: The tendency for individuals with active low back pain to restrict trunk movements may require additional effort to maintain stability. Further research should examine whether trunk restriction is related to pain-related fear of movement and whether additional cognitive resources are required to maintain movement stability.

Structural remodeling of the lumbar multifidus, thoracolumbar fascia and lateral abdominal wall perimuscular connective tissues: A search for its potential determinants.

Recently remodeling of lumbar soft tissues has received increased research attention. However, the major determinants that influence remodeling need to be elucidated in order to understand the impact of different rehabilitation modalities on tissue remodeling. The main aim of this study was to explore the between-subject variance of different measures of lumbar soft tissues quantified with rehabilitative ultrasound imaging (RUSI). RUSI measures (n = 8) were collected from 30 subjects without and 34 patients with LBP: (1) lumbar multifidus (LM) echogenicity (fatty infiltration/fibrosis) at three vertebral levels (L3/L4, L4/L5 and L5/S1) (n = 3); (2) posterior layer thickness of the thoracolumbar fascia (n = 1); and (3) thickness of the fasciae surrounding the external oblique (EO), internal oblique (IO), and transversus abdominis (TrA) (n = 4). Forward stepwise multivariate regression modeling was conducted with these RUSI measures as dependent variables, using the following independent variables as potential determinants: age, sex, the presence of LBP, body size/composition characteristics (height, weight, trunk length, subcutaneous tissue thickness over the abdominal, and LM muscles), trunk muscle function (or activation) as determined with the percent thickness change of LM, EO, IO, and TrA muscles during a standardized effort (RUSI measures), and physical activity level during sport and leisure activities as estimated with a self-report questionnaire. Two or three statistically significant predictors (or determinants) were selected in the regression model of each RUSI measure (n = 8 models), accounting for 26-64% of their total variance. The subcutaneous tissue thickness on the back accounted for 15-30% variance of LM echogenicity measures and thoracolumbar fascia thickness while the subcutaneous tissue thickness over the abdominals accounted for up to 42% variance of the fascia separating the subcutaneous adipose tissues and the EO muscle. The thickness of IO at rest accounted for 13-21% variance of all investigated abdominal fasciae except the fascia separating the subcutaneous adipose tissue and EO. Pain status accounted for 13-18% variance of the anterior and posterior fasciae of the TrA. Age accounted for 11-14% variance of LM echogenicity at all investigated vertebral levels while sex accounted for 15-21% variance of LM echogenicity at L3/L4 and fascia separating subcutaneous adipose tissue and EO muscle. The function (or activation) of EO and LM at L3/L4 accounted for 8-11% variance of the thoracolumbar fascia and fascia separating TrA and intra-abdominal content (TrA posterior fascia), respectively. Finally, the physical activity level during sport activities accounted for 7% variance of the fascia separating the subcutaneous adipose tissues and the EO muscle. These findings suggest that determinants other than body size characteristics may impact the remodeling of lumbar soft tissues, more importantly the subcutaneous adipose tissue deposits (thickness RUSI measures), which are associated with ectopic fat deposition in the LM and in the fasciae that are more closely positioned to the surface. While age, sex, and pain status explain some variability, modifiable factors such as physical activity level as well as trunk muscle thickness and function were involved. Overall, these results suggest that rehabilitation can potentially impact tissue remodeling, particularly in terms of intramuscular and perimuscular adipose tissues.

Structural remodelling of the lumbar multifidus, thoracolumbar fascia and lateral abdominal wall perimuscular connective tissues: A cross-sectional and comparative ultrasound study.

INTRODUCTION: With low back pain (LBP), remodelling of the lumbar soft tissues involves both trunk muscles and neighbouring passive connective tissues. The aim of the present study was to compare three quantitative measures of these tissues, using ultrasound imaging (USI), among healthy controls and individuals with LBP. METHODS: USI measures from 30 healthy subjects and 34 patients with non-acute LBP were compared between groups and sexes. The measures employed were (1) lumbar multifidus echogenicity (fatty/fibrosis infiltration) at three vertebral levels; (2) posterior layer thickness of the thoracolumbar fascia, and (3) thickness of the perimuscular tissues surrounding the external oblique, internal oblique and transversus abdominis (TrA). RESULTS: USI measures of (1) multifidus echogenicity showed statistically significant changes between vertebral levels and sexes (females > males; p = 0.02); (2) differences in thoracolumbar fascia thickness approached statistical significance between groups (LBP > controls; p = 0.09) and sexes (females < males; p = 0.07); and (3) perimuscular tissue surrounding the TrA was significantly thinner (p ≤ 0.001) in patients with LBP compared to controls. DISCUSSION: The thinner perimuscular tissues surrounding the TrA in patients with LBP is a new finding, concurring with previous findings with regard to the lower activation of this deep muscle as well as more recent findings on other perimuscular tissue. CONCLUSION: Overall, USI measures were sensitive to different potential changes (pain status, sex, vertebral level), and this is useful in studying the remodelling of various soft tissues of the trunk.

A Novel Immune Modulator for Patients With Necrotizing Soft Tissue Infections (NSTI): Results of a Multicenter, Phase 3 Randomized Controlled Trial of Reltecimod (AB 103).

BACKGROUND AND OBJECTIVE: Reltecimod, a CD 28 T-lymphocyte receptor mimetic, inhibits T-cell stimulation by an array of bacterial pathogens. A previous phase 2 trial demonstrated improved resolution of organ dysfunction after NSTI. We hypothesized that early administration of reltecimod would improve outcome in severe NSTI. METHODS: Randomized, double-blind, placebo-controlled trial of single dose reltecimod (0.5 mg/kg) administered within 6 hours of NSTI diagnosis at 65 of 93 study sites. Inclusion: surgical confirmation of NSTI and organ dysfunction [modified Sequential Organ Failure Assessment Score (mSOFA) score ≥3]. Primary analysis was modified Intent-to-Treat (mITT), responder analysis using a previously validated composite endpoint, necrotizing infection clinical composite endpoint, defined as: alive at day 28, ≤3 debridements, no amputation beyond first operation, and day 14 mSOFA ≤1 with ≥3 point reduction (organ dysfunction resolution). A prespecified, per protocol (PP) analysis excluded 17 patients with major protocol violations before unblinding. RESULTS: Two hundred ninety patients were enrolled, mITT (Reltecimod 142, Placebo 148): mean age 55 ±â€Š15 years, 60% male, 42.4% diabetic, 28.6% perineal infection, screening mSOFA mean 5.5 ±â€Š2.4. Twenty-eight-day mortality was 15% in both groups. mITT necrotizing infection clinical composite endpoint success was 48.6% reltecimod versus 39.9% placebo, P = 0.135 and PP was 54.3% reltecimod versus 40.3% placebo, P = 0.021. Resolution of organ dysfunction was 65.1% reltecimod versus 52.6% placebo, P = 0.041, mITT and 70.9% versus 53.4%, P = 0.005, PP. CONCLUSION: Early administration of reltecimod in severe NSTI resulted in a significant improvement in the primary composite endpoint in the PP population but not in the mITT population. Reltecimod was associated with improved resolution of organ dysfunction and hospital discharge status.

Orthopedic injuries in patients with multiple injuries: Results of the 11th trauma update international consensus conference Milan, December 11, 2017.

BACKGROUND: In blunt trauma, orthopedic injuries are often associated with cerebral and torso injuries. The optimal timing for definitive care is a concern. The aim of the study was to develop evidence-based guidelines for damage-control orthopedic (DCO) and early total care (ETC) of pelvic and long-bone fractures, closed or open, and mangled extremities in adult trauma patients with and without associated injuries. METHODS: The literature since 2000 to 2016 was systematically screened according to Preferred Reporting Items for Systematic Reviews and meta-analyses protocol. One hundred twenty-four articles were reviewed by a panel of experts to assign grade of recommendation and level of evidence using the Grading of recommendations Assessment, Development, and Evaluation system, and an International Consensus Conference, endorsed by several scientific societies was held. RESULTS: The choice between DCO and ETC depends on the patient's physiology, as well as associated injuries. In hemodynamically unstable pelvic fracture patient, extraperitoneal pelvic packing, angioembolization, external fixation, C-clamp, and resuscitative endovascular balloon occlusion of the aorta are not mutually exclusive. Definitive reconstruction should be deferred until recovery of physiological stability. In long bone fractures, DCO is performed by external fixation, while ETC should be preferred in fully resuscitated patients because of better outcomes. In open fractures early debridement within 24 hours should be recommended and early closure of most grade I, II, IIIa performed. In mangled extremities, limb salvage should be considered for non-life-threatening injuries, mostly of upper limb. CONCLUSION: Orthopedic priorities may be: to save a life: control hemorrhage by stabilizing the pelvis and femur fractures; to save a limb: treat soft tissue and vascular injuries associated with fractures, stabilize fractures, recognize, and prevent compartmental syndrome; to save functionality: treat dislocations, articular fractures, distal fractures. While DCO is the best initial treatment to reduce surgical load, ETC should be applied in stable or stabilized patients to accelerate the recovery of normal functions. LEVEL OF EVIDENCE: Systematic review of predominantly level II studies, level II.